Practice Essentials

Pure red cell aplasia (PRCA) is an uncommon disorder in which maturation arrest occurs in the formation of erythrocytes.
[1, 2] Erythroblasts are virtually absent in bone marrow; however, white blood cell and platelet production are normal. The anemia due to PRCA is usually normocytic but can be macrocytic. In 1922, Kaznelson recognized that this condition was a different entity from aplastic anemia, which presents as pancytopenia.

The characteristics of PRCA (see Workup) include the following:

Severe anemia

Reticulocyte count <1%

The presence of less than 0.5% mature erythroblasts in the bone marrow

Normocellular bone marrow in most cases

The etiology of PRCA is heterogeneous. A congenital form of PRCA was initially described by Joseph in 1936 and by Diamond and Blackfan in 1938. Congenital PRCA is a lifelong disorder and is associated with physical abnormalities.

PRCA can be transient and reversible. Transient erythroblastopenia of childhood (TEC) can occur after viral infections. PRCA due to medications and infections are often reversible.

In adults, most cases of chronic PRCA are idiopathic. Secondary PRCA occurs in patients with conditions such as the following:

The life expectancy of patients with idiopathic PRCA is about 1-2 decades. The survival of patients with congenital PRCA is limited. The lifespan of patients with secondary PRCA depends on the course of the underlying disorder.

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Pathophysiology

In general, pure red cell aplasia (PRCA) is due to a selective injury, often immunological, that affects the early phase of erythrocyte maturation.

Childhood

Diamond-Blackfan syndrome is a rare congenital PRCA that is usually detected at birth, or later during the first 18 months of childhood. Affected individuals usually have a macrocytic anemia. The expression of hemoglobin F and surface “I” antigen in erythrocytes is increased, indicating erythrocyte immaturity.

About one third of these patients have developmental defects, including cleft palates, macroglossia, craniofacial defects, thumb or upper limb abnormalities, cardiac defects, and urogenital malformations. Growth is often retarded.
[2] A modest increased risk for leukemia and neoplasms is noted.

Diamond-Blackfan syndrome is caused by the deletion of genes for ribosomal protein RPS19 in 25% of patients, leading to defects in ribosome biogenesis. This ribosomopathy and haploinsufficiency may be responsible for impaired mRNA translation and the activation of the tumor suppressor gene TP53 in this disorder.
[3, 4, 5, 6, 7, 8]

Germ-line mutations in genes encoding components of both the small (RPS24, RPS17, RPS7, RPS10, and RPS26) and large (RPL35A, RPL5, RPL11, and RPL26) ribosomal subunits have also been described in DBA patients.
[9] Mutations in the GATA1 gene has been found to cause DBA in a minority of patients.
[10] Because GATA1 has been implicated in DBA, it is possible that non-RP genes may also lead to the characteristic erythroid hypoplasia.
[9]

De novo cases of Diamond-Blackfan syndrome are believed to be caused by intrauterine damage to early erythroid stem cells.
[11] A familial history of PRCA is evident in approximately 10% of patients.

Transient erythroblastopenia of childhood (TEC) is a self–limiting, benign disorder. A history of a recent viral infection is usually noted.
[12] Parvovirus 19 infection should be ruled out.

Adults

Acquired primary (idiopathic) PRCA is the most common form of red cell aplasia in adults.

However, PRCA can be secondary to underlying disorders. For example, autoimmune disorders (eg, type 1 diabetes, thyroiditis, rheumatoid arthritis, Sjögren syndrome) can be responsible. PRCA has been shown to be secondary to T-cell inhibition of marrow erythroid cells. PRCA can also be secondary to and is associated with the following:

The incidence of PRCA has increased in patients with chronic renal disease who have received epoetin therapy. This has been ascribed to the generation of antiepoetin antibodies, which occurs more often with epoetin-alpha than with epoetin-beta. This complication may be avoided by using an erythropoietin-mimicking human antibody, which stimulates erythropoiesis but does not appear to induce antiepoetin antibodies and PRCA.
[15, 16, 17]

Originally, thymoma was cited as the primary cause of acquired PRCA. However, subsequent studies have revealed that only a small percent of all cases of PRCA result from thymomas. Conversely, only 7% of patients with thymomas had PRCA.

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Epidemiology

Pure red cell aplasia (PRCA) is an uncommon disorder. The idiopathic form is the most common type of PRCA. The incidence of transient and reversible PRCA that occurs in childhood and in adults secondary to medications and infections is probably underestimated. The reason for this underestimation is the anemia is self-limiting. Acquired secondary PRCA is not common. Diamond-Blackfan syndrome is rare.

No racial, age, or sex predilection is reported in PRCA. However, females are more likely to have autoimmune disorders.

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Prognosis

Prognosis varies among the different types of pure red cell aplasia (PRCA).

Transient erythroblastopenia and other PRCA disorders in children and adults are benign with an excellent prognosis.

The prognosis of secondary PRCA depends on the course of the underlying condition, such as a thymoma or a hematological malignancy. About 30% of PRCA cases due to thymomas are reversed by thymectomy.

Most cases of PRCA are idiopathic. About 68% respond to intervention. However, relapses are common. The lifespan of these patients is about 1-2 decades.

Most patients with Diamond-Blackfan syndrome respond to corticosteroid therapy but are prone to relapses. Estimating the lifespan of patients with this disorder is difficult because it is rare.

Prognosis is also influenced by the complications of therapy. Hemosiderosis can develop in multitransfused patients. Corticosteroid therapy can lead to osteopenia and osteoporosis and infections. PRCA can evolve into aplastic anemia and acute myelogenous leukemia, which have high morbidity and mortality rates. Infections acquired during blood product transfusions can also affect prognosis.